Naturally Occurring Siderophores

Aside from opening a pore, the easiest method to transport material from one side of a phospholipid bilayer to the other is to design small molecules that mimic naturally occurring siderophores or ionophores. 

Naturally occurring and synthetically accessible siderophores (iron carriers) contain predominantly bidentate pyrocatechinato- or hydroxamato ligands and are of special interest because of their high affinity towards trivalent metal ions, especially towards iron(III) ions [5, 118-127]. The methyl ( )-2-(l-alkyl/aryl-4,5-dihydro-l//-tetrazol-5-ylidene)-2-cyanoacetates 41a-c, first prepared by us [128], also appeared to be suitable as siderophores. 

The chromic-substituted siderophore complexes can be prepared and, in contrast to the naturally occurring ferric complexes, are kinetic-ally inert to isomerization or ligand substitution. 

Siderophores,hexadentate tris-catecholate and tris-hydroxamate ligands, are produced by many microorganisms to facihtate iron uptake. Several synthetic models, such as trencam (35) and licams (36), for the tris-catecholate enterobactin (37) do not quite match its affinity for iron(ni) (Table 8). Similar tris-hydroxamate ligands model naturally occurring ferrichromes and desferrioxamines (e g. dfo, (38)). 

A comparison of the stability constants of the naturally occurring siderophores uncovers a difference of f7 orders of magnitude between enterobactin (K most stable hydroxamate complex, ferrioxamine E. Using the more comparable pM values, enterobactin remains stiU eight orders of magnitude more effective than ferrioxamine E. Enterobactin has the highest affinity for Fe ion of any biological iron chelator tested so far. 

Deferoxamine is a polyhydroxamine acid with specific affinity for iron and, less strongly, aluminium. It is a naturally occurring siderophore produced by Streptomyces pilosus. 

Figure 6.18. MacrcKyclic complex fonners. (a) Structure of a ferrichrome (desferri-ferrichrome), one of the strongest complex formers presently known for Fe(III). The iron-binding center is an octahedral arrangement of six oxygen donor atoms of trihy-droxamate. Such naturally occurring ferrichromes play an important role in the biosynthetic pathways involving iron. Complexing functionalities of some biogenic ligands (b) hydroxamate siderophores, (c) catechol siderophores, and (d) phytochelatines. For detailed structures see Neilands (1981).

A significant effort has been made to prepare ligands with high specific affinity and selectivity for actinides that could be used for mammalian chelation therapy or as a specific extractant. A biomimetic approach to such ligand design, based on naturally occurring hydroxamate and catecholate siderophores and hydroxypyridinoate moieties, has been the most vital. The actinide... 

A linear bis(catecholamide), analogue of the naturally occurring siderophore (40), has been synthesized by the azolide method and its complexation with molybdenum investigated.51 Thermodynamic and kinetic studies on the flexible ligand (41), able to form a homochiral Fe2(41)3 dinuclear iron(II) complex, were undertaken for a better understanding of the self-assembling processes.52... 

In the last three decades more than 80 naturally-occurring siderophores have been isolated and characterized. Since their structural features and their biological role have been extensively and comprehensively reviewed 10> I9,20 26 29) we will focus in this section only on a selection of the main representatives in order to point out the wide range of ligands which are produced by microorganisms to obtain iron from the environment (Fig. 1 and 2). 

Since there are some naturally-occurring antibiotics such as the albomycins, which contain the structural features of the siderophores with an appended antibiotic functional unit61,62, synthetic or derivative siderophores may be important new antibiotics 63). In principle these are very effective, since the siderophore antibiotics are recognized as species-generated iron transport agents at the membrane receptor site of producing microorganisms 64). 

Siderophores are naturally occurring chelate compounds synthesized by microorganisms and used to sequester the biologically essential but sparingly soluble ferric ion from their solution environment (1, 2,. The close relationship between microbial... 

A comparison of the stability constants of the naturally occurring siderophores uncovers a difference of 17 orders of magnitude between enterobactin K and the... 

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